Biomedical subjects

B Zumoff

Publications and source records attributed to B Zumoff.

166 records · Page 10Linked to original sources

PubMedDate not supplied

Hormonal profiles in women with breast cancer (review).

The literature concerning endogenous hormonal profiles in women with breast cancer and breast-cancer risk has been critically reviewed. The many published reports have been divided into 11 groups, with each group centered on a particular hypothesis that has been either explicitly formulated by the authors of the reports or perceived by other workers as a unifying hypothesis in certain studies. The hypotheses reviewed are: the adrenal androgen insufficiency hypothesis, the anovulation/luteal inadequacy hypothesis, the estriol hypothesis, the ovarian androgen excess hypothesis, the thyroid dysfunction hypothesis, the prolactin hypothesis, the estrone hypothesis, the estrogen-window hypothesis, the estrogen-excess hypothesis, the melatonin hypothesis, and the estrogen hydroxylation hypothesis. It is concluded that there remain, at present, only four viable hypotheses: the hypotheses of increased risk with adrenal androgen deficiency, ovarian dysfunction (luteal inadequacy and excessive ovarian androgen secretion), increased 16 alpha-hydroxylation of estradiol, and the hypothesis of decreased risk with pregnancy-induced lowering of prolactin levels. Adrenal androgen deficiency seems to be pertinent only in premenopausal cancer patients, and may be a genetic defect. Ovarian dysfunction seems to be pertinent to both premenopausal and post-menopausal patients and may also have a strong genetic component. Increased estradiol hydroxylation likewise seems to have a genetic component. The prolactin effect differs from the others, in that it is clearly environmental, rather than genetic, and may represent a permissive effect rather than a true risk-promoting effect.

Breast Neoplasms↗

PubMedDate not supplied

Nonobesity at the time of mastectomy is highly predictive of 10-year disease-free survival in women with breast cancer.

25 unselected women with operable breast cancer were followed after radical mastectomy until they died of recurrent cancer (non-survivors), or for 10 years if there was no recurrence (survivors): all the women still alive at 10 years were clinically and radiographically disease-free. Survivors and non-survivors were compared with respect to premastectomy height, and deviation from ideal weight. There were 16 women in the survivor group; at the time of mastectomy, they averaged 11% above ideal weight and only 4 of them (25%) were obese (20% or more above ideal weight). There were 9 women in the non-survival group; they averaged 51% above ideal weight at the time of mastectomy and all of them were obese, as defined. The intergroup difference in mean deviation from ideal weight was very highly significant (P less than 0.0001). Of the 13 women who were obese at mastectomy, only 4 (31%) became survivors, while 100% of the 12 women who were non-obese at mastectomy became survivors; the difference in percent survival was very highly significant (P less than 0.005). Separate evaluation of the roles of height and weight showed that height was not a factor and weight accounted entirely for the observed differences. It appears that maintenance of nonobesity may be a more effective way of decreasing mortality from breast cancer than any other measure proposed to date.

Adult↗

PubMedDate not supplied

Effect of tamoxifen treatment on estrogen metabolism in postmenopausal women with advanced breast cancer.

The effect of tamoxifen therapy on plasma estrone and estradiol concentration, urinary excretion of estrone, estradiol, and estriol glucuronides, and metabolism of a tracer of 3H-estradiol was studied in 12 postmenopausal women with metastatic breast cancer. The most striking change observed was consistent increase in the 72-hour urinary recovery of total radioactivity after the tracer, from a mean of 47% to a mean of 61% of the dose. This increase was accounted for by a corresponding increase in the recovery of total glucuronide radioactivity, from a mean of 32% to a mean of 44% of the dose; there was no change in the proportions of estrone, estradiol, estriol, or 2-hydroxyestrone in the glucuronide fraction. The most likely explanation for this finding is that the estrogen-receptor-blocking effect of tamoxifen decreases estrogen uptake by various tissues and permits the estrogen to be excreted in the urine instead. There was also a small but consistent and significant decrease in plasma estrone (from 47 to 36 pg/ml) and estradiol (from 15 to 13 pg/ml), with no change in urinary excretion of estrogen glucuronides. The drop in plasma estrogen levels without a decrease in estrogen production suggests that tamoxifen may increase the metabolic and/or renal clearance of estrogen metabolites. There was no correlation between the observed effects of tamoxifen and the pretreatment estrogen-receptor status of the patient or her response to tamoxifen therapy.

Aged↗

PubMedDate not supplied

Abnormal production of androgens in women with breast cancer.

Two long and broad streams of medical literature, from the 1950's to date, have established the existence of two unrelated abnormalities of androgen production in women with breast cancer. One is the genetically determined presence of subnormal production of adrenal androgens (i.e. DHEA and DHEAS) in women with premenopausal breast cancer and their sisters, who are at increased risk for breast cancer. The other is excessive production of testosterone, of ovarian origin, in subsets of women with either premenopausal or postmenopausal breast cancer and women with atypical breast-duct hyperplasia, who are at increased risk for breast cancer; along with the hypertestosteronism, there is frequently chronic anovulation in the premenopausal patients. The combination of ovarian hypertestosteronism and chronic anovulation is characteristic of the polycystic ovary syndrome and is also frequently seen in women with abdominal ("android") obesity; both PCOS and abdominal obesity are known to be characterized by high risk for postmenopausal cancer. The elevated testosterone levels and the increased levels of insulin, IGF-I, and IGF-II that are seen in PCOS and abdominal obesity could favor the development of breast cancer in several ways, all of which have been demonstrated experimentally: binding of testosterone to cancer cells bearing testosterone receptors, with direct stimulation; intratissular aromatization of testosterone to estradiol, with stimulation of estrogen-sensitive cells; stimulation of the production of epithelial growth factor (EGF) by testosterone, with direct mitogenic effect of EGF on cancer cells; stimulation of aromatase by insulin and IGF-I; direct mitogenic stimulation of cancer cells by insulin, IGF-I, and IGF-II; and stimulation by IGF-I and IGF-II of the intratissular reduction of estrone to estradiol. Since PCOS is probably largely genetically determined, and abdominal obesity may also be, the hypertestosteronism of these conditions may represent a second genetically determined hormonal risk factor for breast cancer.

Adrenal Glands↗